1. Field of the Invention
This invention relates to intravascular balloon catheters and, in particular, the use of ionizing radiation for the sterilization of such devices.
2. Background Art
Surgical procedures employing balloons and medical devices incorporating those balloons (i.e., balloon catheters) have become routine. These procedures, such as angioplasty procedures, are conducted on narrow or obstructed openings in blood vessels, and other passageways in the body, to increase the flow through the obstructed areas. For example, in an angioplasty procedure, a dilatation balloon catheter is used to enlarge or open an occluded blood vessel which is partially restricted or obstructed due to the existence of a hardened stenosis or buildup within the vessel. This procedure requires that a balloon catheter be inserted into the patient's body and positioned within the vessel so that the balloon, when inflated, will dilate the site of the obstruction or stenosis so that the obstruction or stenosis is minimized, thereby resulting in increased blood flow through the vessel.
Measurable characteristics of balloons in general, and more specifically of dilatation balloons, include distensibility (the percent radial expansion with increased pressure), elastic stress response (repeatability of obtaining the same diameter at the same pressure during repeated inflation-deflation cycles), flexibility, tensile strength and optical clarity.
Polymeric materials are increasingly being used to manufacture balloons, particularly dilatation balloons. It has been found that balloons can be formed by processing a polymeric material composed of polymer chains having sufficient regions of molecular structure with inter-molecular chain interaction to ensure the integrity and strength of the structure, as well as sufficient regions which permit sections of the polymer chains to “uncoil” to permit growth. Such balloons are (i) sufficiently distensible (i.e., about 5 to about 20%) to allow treatment of various sized arteries, (ii) have a high degree of elastic stress response (i.e., less than about 5.00), which permits the physician to treat multiple stenosis within the same artery without having to be concerned with increasing balloon diameter after repeated inflations, and (iii) have strength sufficient to treat hardened stenosis (i.e., greater than about 14,000 psi). Therefore, balloons formed by such methods have an overall advantageous combination of these physical properties i.e., distensibility, elastic stress response and tensile strength, that are superior to those exhibited by other balloons of the related art. The sterilization method of the present invention may be used with balloons made from any material that is degraded by radiation doses typically used in ionizing radiation sterilization.
While the foregoing properties are desirable in balloons, these attributes are typically adversely affected by the sterilization process which all balloons and balloon catheters must be subjected to prior to use in the human body. For example, when a balloon is exposed to a traditional sterilization process (e.g., humidity of 60±15%, temperature of about 45±5° C., 100% ethylene oxide for approximately 12-16 hours) the balloon tends to shrink, which causes a corresponding increase in wall thickness. This increase in wall thickness will adversely affect the folded profile of the sterilized balloon product. Furthermore, the distensibility of many balloons is adversely affected by the sterilization processes currently used in the art. Therefore, it is desirable that any sterilization process used to treat balloons and balloon catheters provide adequate sterilization, while at the same time not adversely affecting the physical characteristics of the finished balloon or balloon catheter product.
Ethylene oxide sterilization is one method for sterilization of heat-sensitive or moisture-sensitive medical instruments including dilatation balloons and dilatation balloon catheters. However, there are several disadvantages to using ethylene oxide as a method for sterilization. Ethylene oxide is highly flammable and explosive in air and must be used in an explosion-proof sterilizing chamber in a controlled environment. Ethylene oxide is also readily absorbed by many polymers and is not always easily desorbed or eliminated. Toxic emissions and residues of ethylene oxide present hazards to personnel, patients and the environment. Furthermore, the processing conditions employed during the ethylene oxide sterilization process can alter the composition and morphology of some polymeric materials, and hence their mechanical properties.
Sterilization of polymeric medical devices by ionizing radiation is increasingly being employed as an alternative to gaseous ethylene oxide sterilization. The term ionizing radiation is used to designate the emission of electrons or highly accelerated, relatively heavy, nuclear particles such as protons, neutrons, alpha particles, deuterons, beta particles, or their analogs, directed in such a way that the particle is projected into the mass to be irradiated. Radiation sterilization includes the use of ultraviolet rays, electron beams, x-rays, gamma rays, and to a limited extent, gas plasma and microwave radiation. Sterilization by ionizing radiation is usually carried by using either gamma radiation, from Cobalt or Cesium sources, or electron beam (E-beam) irradiation. One difference between the two sources is the dose rate or exposure time over which the dose is delivered. The dose rate for E-beam irradiation can be as high as 20 kGy/s compared to 1-10 kGy/hrs for Gamma radiation. Hence the exposure times are often considerably shorter for E-beam sterilization than for sterilization by gamma radiation.
Sterilization by ionizing radiation is a consequence of the high-energy electrons released from the interaction of Gamma-ray photons or electron-beam particles with the material being sterilized. Depending on the energy of radiation many secondary electrons and free radicals can be created in the vicinity of the original interaction site. The cascade is propagated until all the excess energy above the ionization threshold is dissipated. Thus, from a single incoming photon or electron, a shower of secondary electrons is generated. These high-energy electrons permanently alter the DNA sequences in the microbiological species, rendering them innocuous.
However, the high-energy photons and electrons can also initiate unwanted ionization events in polymeric material during sterilization. The effects vary greatly with the chemical structure of the polymer and the employed dose of radiation. Alterations in molecular structure, caused by the ionization processes, are manifested as changes in physical and mechanical properties of the polymer. The two major mechanisms of degradation that occur during the irradiation process are: (1) chain scission of the polymer molecule resulting in a reduction in molecular weight and (2) cross-linking of the polymer molecules which can lead to the formation of three dimensional network structures. The chemical composition of the polymer largely dictates the degradation mechanism, although the two mechanisms can sometimes occur simultaneously with the final properties being dictated by the net-effect.
The degradation process is initiated when high-energy radiation interacts with the hydrocarbon polymeric molecule to generate macro-radicals, shown in the following reaction, where R—H is the polymer molecule and R•is the “cleaved” polymer chain which forms during irradiation:
Polymeric macro-radicals (R•) rapidly combine with environmental oxygen, which is a very efficient radical scavenger, to form peroxide radicals as shown by the following reaction:
Polymeric peroxide radicals (RO2•) can then react with another hydrocarbon polymeric molecule to further propagate the degradation process:RO2•+R—H→ROOH+R•  Step 3: PropagationWhilst a polymeric macro-radical (R•) can react again with oxygen as in step 2, the hydroperoxide (ROOH) may also decompose to form additional radicals, thus propagating the degradation process further:ROOH→RO•+•OH  Step 4: PropagationAs a result of the auto-catalytic nature of the oxidation process, a single primary event can lead to extensive damage by generating a cascade of radicals from the initial radicals created during the irradiation process.
In relation to the sterilization of polymeric materials, ionizing irradiation has been found to have a negative impact on the properties of dilatation balloons manufactured from certain polymers, such as polyamide block copolymers. Resultant physical changes can include embrittlement, discoloration, odor generation, stiffening, softening, enhancement of chemical resistance, and an increase or decrease in melt temperature. Various high-performance stabilizers have been found to be ineffective in preserving the physical properties of these polymers, probably due to high rates of the degradation reactions. Therefore, alternative methods and devices are needed to minimize the damage caused by ionizing radiation during sterilization of susceptible polymers.